Allosteric Modulator (PAM/NAM)

A ligand that binds to a site on a receptor distinct from the orthosteric (active) site, altering receptor conformation to either enhance (positive allosteric modulator, PAM) or diminish (negative allosteric modulator, NAM) the response to endogenous or exogenous agonists. Allosteric modulators preserve the temporal and spatial signaling patterns of endogenous ligands, potentially offering improved selectivity and reduced side effects compared to orthosteric agents.

Примеры

• Benzodiazepines: PAMs at GABA-A receptors, enhancing chloride channel opening frequency
• Cinacalcet: PAM at calcium-sensing receptors for secondary hyperparathyroidism
• Maraviroc: NAM at CCR5 coreceptor, preventing HIV entry